We propose to study the basic mechanisms of the immune response and some of the many factors regulating this essential function. We will use several approaches to investigate how antigen stimulates the differentiation and proliferation of antigen reactive cells and of antibody producing cells and what essential interactions specific cells must undergo for the development of immune responses. These approaches are: A) The identification of the process determined by dominant autosomal genes which have been shown to control specific immune responses. B) The analysis of immune responses to hapten-protein antigens, where cellular cooperation between carrier specific and hapten specific cells has been demonstrated to enhance anti-hapten antibody synthesis. C) The study of tolerance induction to hapten-protein conjugates. BIBLIOGRAPHIC REFERENCES: Kapp, J.A., Pierce, C.W., de la Croix, F., and Benacerraf, B.: Immunosuppressive factor(s) extracted from lymphoid cells of nonresponder mice primed with L-glutamic acid 60-L-alanine 30-L-tyrosine 10 (GAT). I. Activity and antigenic specificity. J. Immunol. 116: 305, 1976. Dorf, M.E., Maurer, P.H., Merryman, C.F., and Benacerraf, B.: Inclusion group systems and cis-trans effects in responses controlled by the two complementing Ir-GLo genes. J. Exp. Med. 143: 889, 1976.